• A L Krarup, L Ny, M Astrand, A Bajor, F Hvid-Jensen, M B Hansen, M Simrén, P Funch-Jensen, and A M Drewes.
• Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
• Aliment. Pharmacol. Ther. 2011 May 1;33(10):1113-22.

BackgroundMany patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor 'transient receptor potential vanilloid 1'(TRPV1) are a potential drug class for GERD treatment.AimTo investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain.MethodsTwenty-two healthy men (20-31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli.Data Analysisintention-to-treat.ResultsA total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10-38%] and 28%, respectively (CI: 14-43%). The skin heat tolerance was increased 2.1 °C (CI: 1.1-3.2 °C) after 30 mg AZD1386 and 4.0 °C (CI: 3.0-5.0 °C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported 'feeling cold' and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4±0.3 °C and 0.7±0.3 °C, respectively, P<0.05).ConclusionsAZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD.© 2011 Blackwell Publishing Ltd.

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